Universal field matching in craniospinal irradiation by a background-dose gradient-optimized method

Purpose: The gradient-optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient-optimized technique, based on the use of a background dose, is described. Methods: Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An 'in silico' ideal background dose was created first to cover the upper-spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower-spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper-spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on. Results: In both proton and photon plans, the optimized cranial and the lower-spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper-spinal beam. The final dose distributions showed a homogeneous coverage of the targets. Discussion: Our simple technique allowed to obtain high-quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose

Investigation of corrosion-erosion phenomena in the primary cooling system of SPIDER

SPIDER dedicated cooling plant has to remove up to 10 MW thermal power from in-vessel components and auxiliary systems. The circuit is characterized by three main heat transfer systems: primary, secondary and tertiary systems. The primary system is made of four circuits, with only three operating so far, these are called PC01, PC02 and PC03. These three circuits respectively cool SPIDER power supplies and the beam source components using ultrapure water. During 2019 SPIDER experimental campaigns, it was observed that electrical resistivity of water degraded considerably and more quickly (∼25 MΩ cm h−1 in PC01) than estimated by design. To overcome this issue, water had to be restored very frequently to maintain the desired characteristics and avoid possible detrimental leakage currents throughout the circuit. The reason for this severe water degradation has to be better understood before issues such as abrupt failures may arise. This work presents a preliminary analysis of the two main circuits (PC01 and PC02) where an estimation of water degradation induced by general corrosion of stainless steels and copper components was made. This preliminary estimation showed that PC01 could be more prone to general corrosion than PC02; however, the rate of water conductivity increase was 5.3 times smaller than that observed during experiments in 2019 and 2020

3-D kinematic comparison of treadmill and overground running.

Studies investigating the mechanics of human movement are often conducted using the treadmill. The treadmill is an attractive device for the analysis of human locomotion. Studies comparing overground and treadmill running have analyzed discrete variables, however differences in excursion from footstrike to peak angle and range of motion during stance have yet to be examined. This study aimed to examine the 3-D kinematics of the lower extremities during overground and treadmill locomotion to determine the extent to which the two modalities differ. Twelve participants ran at 4.0m/s in both treadmill and overground conditions. 3-D angular kinematic parameters during the stance phase were collected using an eight camera motion analysis system. Hip, knee and ankle joint kinematics were quantified in the sagittal, coronal and transverse planes, then compared using paired t-tests. Of the parameters analyzed hip flexion at footstrike 12° hip range of motion 17°, peak hip flexion 12.7°, hip transverse plane range of motion 8° peak knee flexion 5° and peak ankle excursion range 6.6°, coronal plane ankle angle at toe-off 6.5° and peak ankle eversion 6.3° were found to be significantly different. These results lead to the conclusion that the mechanics of treadmill locomotion cannot be generalized to overground

Birth and closure of the Kallipetra Basin: Late Cretaceous reworking of the Jurassic Pelagonian-Axios/Vardar contact (northern Greece)

Some 20 Myr after the Late Jurassic to Early Cretaceous obduction and collision at the eastern margin of Adria, the eroded Pelagonia (Adria) Axios/Vardar (oceanic complex) contact collapsed, forming the Kallipetra Basin, described around the Aliakmon River near Veroia (northern Greece). Clastic and carbonate marine sediments deposited from the early Cenomanian to the end of the Turonian, with abundant olistoliths and slope failures at the base due to active normal faults. The middle part of the series is characterized by red and green pelagic limestones, with a minimal contribution of terrigenous debris. Rudist mounds in the upper part of the basin started forming on the southwestern slope, and their growth competed with a flux of ophiolitic debris, documenting the new fault scarps affecting the Vardar oceanic complex (VOC). Eventually, the basin was closed by overthrusting of the VOC towards the northeast and was buried and heated up to ~ 180 °C. A strong reverse geothermal gradient with temperatures increasing up-section to near 300 °C is recorded beneath the VOC by illite crystallinity and by the crystallization of chlorite during deformation. This syntectonic heat partially reset the zircon fission track ages bracketing the timing of closure just after the deposition of the ophiolitic debris in the Turonian. This study documents the reworking of the Pelagonian Axios/Vardar contact, with Cenomanian extension and basin widening followed by Turonian compression and basin inversion. Thrusting occurred earlier than previously reported in the literature for the eastern Adria and shows a vergence toward the northeast, at odds with the regional southwest vergence of the whole margin but in accordance to some reports about 50 km north

Modal Gating of Human CaV2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits

The single channel gating properties of human CaV2.1 (P/Q-type) calcium channels and their modulation by the auxiliary β1b, β2e, β3a, and β4a subunits were investigated with cell-attached patch-clamp recordings on HEK293 cells stably expressing human CaV2.1 channels. These calcium channels showed a complex modal gating, which is described in this and the following paper (Fellin, T., S. Luvisetto, M. Spagnolo, and D. Pietrobon. 2004. J. Gen. Physiol. 124:463–474). Here, we report the characterization of two modes of gating of human CaV2.1 channels, the slow mode and the fast mode. A channel in the two gating modes differs in mean closed times and latency to first opening (both longer in the slow mode), in voltage dependence of the open probability (larger depolarizations are necessary to open the channel in the slow mode), in kinetics of inactivation (slower in the slow mode), and voltage dependence of steady-state inactivation (occurring at less negative voltages in the slow mode). CaV2.1 channels containing any of the four β subtypes can gate in either the slow or the fast mode, with only minor differences in the rate constants of the transitions between closed and open states within each mode. In both modes, CaV2.1 channels display different rates of inactivation and different steady-state inactivation depending on the β subtype. The type of β subunit also modulates the relative occurrence of the slow and the fast gating mode of CaV2.1 channels; β3a promotes the fast mode, whereas β4a promotes the slow mode. The prevailing mode of gating of CaV2.1 channels lacking a β subunit is a gating mode in which the channel shows shorter mean open times, longer mean closed times, longer first latency, a much larger fraction of nulls, and activates at more positive voltages than in either the fast or slow mode

Enhanced Astrocytic Ca\u3csup\u3e2+\u3c/sup\u3e Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca2+ signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal death in vivo. Using two-photon microscopy in vivo, we show that status epilepticus enhances astrocytic Ca2+ signals for 3 d and that the period of elevated glial Ca2+ signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca2+ signals in vivo, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca2+ chelators selectively into astrocytes after status epilepticus.We demonstrate that the selective attenuation of glial Ca2+ signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target

Start of SPIDER operation towards ITER neutral beams

Heating Neutral Beam (HNB) Injectors will constitute the main plasma heating and current drive tool both in ITER and JT60-SA, which are the next major experimental steps for demonstrating nuclear fusion as viable energy source. In ITER, in order to achieve the required thermonuclear fusion power gain Q=10 for short pulse operation and Q=5 for long pulse operation (up to 3600s), two HNB injectors will be needed [1], each delivering a total power of about 16.5 MW into the magnetically-confined plasma, by means of neutral hydrogen or deuterium particles having a specific energy of about 1 MeV. Since only negatively charged particles can be efficiently neutralized at such energy, the ITER HNB injectors [2] will be based on negative ions, generated by caesium-catalysed surface conversion of atoms in a radio-frequency driven plasma source. A negative deuterium ion current of more than 40 A will be extracted, accelerated and focused in a multi-aperture, multi-stage electrostatic accelerator, having 1280 apertures (~ 14 mm diam.) and 5 acceleration stages (~200 kV each) [3]. After passing through a narrow gas-cell neutralizer, the residual ions will be deflected and discarded, whereas the neutralized particles will continue their trajectory through a duct into the tokamak vessels to deliver the required heating power to the ITER plasma for a pulse duration of about 3600 s. Although the operating principles and the implementation of the most critical parts of the injector have been tested in different experiments, the ITER NBI requirements have never been simultaneously attained. In order to reduce the risks and to optimize the design and operating procedures of the HNB for ITER, a dedicated Neutral Beam Test Facility (NBTF) [4] has been promoted by the ITER Organization with the contribution of the European Union\u2019s Joint Undertaking for ITER and of the Italian Government, with the participation of the Japanese and Indian Domestic Agencies (JADA and INDA) and of several European laboratories, such as IPP-Garching, KIT-Karlsruhe, CCFE-Culham, CEA-Cadarache. The NBTF, nicknamed PRIMA, has been set up at Consorzio RFX in Padova, Italy [5]. The planned experiments will verify continuous HNB operation for one hour, under stringent requirements for beam divergence (< 7 mrad) and aiming (within 2 mrad). To study and optimise HNB performances, the NBTF includes two experiments: MITICA, full-scale NBI prototype with 1 MeV particle energy and SPIDER, with 100 keV particle energy and 40 A current, aiming at testing and optimizing the full-scale ion source. SPIDER will focus on source uniformity, negative ion current density and beam optics. In June 2018 the experimental operation of SPIDER has started

ATP signalling in epilepsy

This paper focuses on a role for ATP neurotransmission and gliotransmission in the pathophysiology of epileptic seizures. ATP along with gap junctions propagates the glial calcium wave, which is an extraneuronal signalling pathway in the central nervous system. Recently astrocyte intercellular calcium waves have been shown to underlie seizures, and conventional antiepileptic drugs have been shown to attenuate these calcium waves. Blocking ATP-mediated gliotransmission, therefore, represents a potential target for antiepileptic drugs. Furthermore, while knowledge of an antiepileptic role for adenosine is not new, a recent study showed that adenosine accumulates from the hydrolysis of accumulated ATP released by astrocytes and is believed to inhibit distant synapses by acting on adenosine receptors. Such a mechanism is consistent with a surround-inhibitory mechanism whose failure would predispose to seizures. Other potential roles for ATP signalling in the initiation and spread of epileptiform discharges may involve synaptic plasticity and coordination of synaptic networks. We conclude by making speculations about future developments

A qualitative examination of inappropriate hospital admissions and lengths of stay

<p>Abstract</p> <p>Background</p> <p>Research has shown that a number of patients, with a variety of diagnoses, are admitted to hospital when it is not essential and can remain in hospital unnecessarily. To date, research in this area has been primarily quantitative. The purpose of this study was to explore the perceived causes of inappropriate or prolonged lengths of stay and focuses on a specific population (i.e., patients with long term neurological conditions). We also wanted to identify interventions which might avoid admission or expedite discharge as periods of hospitalisation pose particular risks for this group.</p> <p>Methods</p> <p>Two focus groups were conducted with a convenience sample of eight primary and secondary care clinicians working in the Derbyshire area. Data were analysed using a thematic content approach.</p> <p>Results</p> <p>The participants identified a number of key causes of inappropriate admissions and lengths of stay, including: the limited capacity of health and social care resources; poor communication between primary and secondary care clinicians and the cautiousness of clinicians who manage patients in community settings. The participants also suggested a number of strategies that may prevent inappropriate admissions or reduce length of stay (LoS), including: the introduction of new sub-acute care facilities; the introduction of auxiliary nurses to support specialist nursing staff and patient held summaries of specialist consultations.</p> <p>Conclusion</p> <p>Clinicians in both the secondary and primary care sectors acknowledged that some admissions were unnecessary and some patients remain in hospital for a prolonged period. These events were attributed to problems with the current capacity or structuring of services. It was noted, for example, that there is a shortage of appropriate therapeutic services and that the distribution of beds between community and sub-acute care should be reviewed.</p